Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status
The nature of age-related changes in cholinergic function and their relationship to age-related behavioral decline were examined in the present study. Male Fischer-344 rats of four ages (four, 11, 17 and 23 months) were tested in a battery of cognitive tasks. Discrete microdissections of brain areas...
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| Veröffentlicht in: | Neuroscience 1999-03, Vol.89 (3), p.771-780 |
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| creator | Baxter, M.G Frick, K.M Price, D.L Breckler, S.J Markowska, A.L Gorman, L.K |
| description | The nature of age-related changes in cholinergic function and their relationship to age-related behavioral decline were examined in the present study. Male Fischer-344 rats of four ages (four, 11, 17 and 23
months) were tested in a battery of cognitive tasks. Discrete microdissections of brain areas involved in cognitive function were performed, and activity of choline acetyltransferase and levels of hemicholinium-3 binding were determined to assess the integrity of cholinergic innervation. Age-related changes in cholinergic markers occurred predominantly in the medial septal area and its target areas (hippocampus and cingulate cortex), and were also present in the posterior caudate. However, most of the age-related changes in cholinergic markers were already present at ages at which behavioral impairment was not yet maximal. There were some consistent correlations between behavioral and neurochemical measures, independent of age, but these accounted for relatively small proportions of variance in behavioral performance. For most of these correlations, lower levels of presynaptic cholinergic markers were related to better behavioral performance. In brain areas in which correlations changed with age, lower levels of presynaptic cholinergic markers were associated with better performance in young rats, whereas higher levels were associated with better performance in aged rats.
Recent lesion studies using a toxin selective for basal forebrain cholinergic neurons have suggested that these neurons do not play as central a role in learning and memory in young and aged animals as was previously thought. When considered in this context, the present results suggest that preserved cholinergic function in old age might act indirectly to sustain cognitive ability. Changes in cholinergic function may represent one of a number of age-related neurobiological events that underlie behavioral impairments, or may be a permissive factor for other age-related processes that are more directly responsible for cognitive impairments. |
| doi_str_mv | 10.1016/S0306-4522(98)00374-1 |
| format | Article |
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months) were tested in a battery of cognitive tasks. Discrete microdissections of brain areas involved in cognitive function were performed, and activity of choline acetyltransferase and levels of hemicholinium-3 binding were determined to assess the integrity of cholinergic innervation. Age-related changes in cholinergic markers occurred predominantly in the medial septal area and its target areas (hippocampus and cingulate cortex), and were also present in the posterior caudate. However, most of the age-related changes in cholinergic markers were already present at ages at which behavioral impairment was not yet maximal. There were some consistent correlations between behavioral and neurochemical measures, independent of age, but these accounted for relatively small proportions of variance in behavioral performance. For most of these correlations, lower levels of presynaptic cholinergic markers were related to better behavioral performance. In brain areas in which correlations changed with age, lower levels of presynaptic cholinergic markers were associated with better performance in young rats, whereas higher levels were associated with better performance in aged rats.
Recent lesion studies using a toxin selective for basal forebrain cholinergic neurons have suggested that these neurons do not play as central a role in learning and memory in young and aged animals as was previously thought. When considered in this context, the present results suggest that preserved cholinergic function in old age might act indirectly to sustain cognitive ability. Changes in cholinergic function may represent one of a number of age-related neurobiological events that underlie behavioral impairments, or may be a permissive factor for other age-related processes that are more directly responsible for cognitive impairments.</description><identifier>ISSN: 0306-4522</identifier><identifier>EISSN: 1873-7544</identifier><identifier>DOI: 10.1016/S0306-4522(98)00374-1</identifier><identifier>PMID: 10199612</identifier><identifier>CODEN: NRSCDN</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>acetylcholine ; Acetylcholine - physiology ; ageing ; Aging - physiology ; Animals ; basal forebrain ; Biological and medical sciences ; Biomarkers ; Brain Chemistry ; Choline O-Acetyltransferase - analysis ; Cholinergic Agents - metabolism ; Cognition - physiology ; Cognition Disorders - physiopathology ; Development. Senescence. Regeneration. Transplantation ; Fundamental and applied biological sciences. Psychology ; hemicholinium 3 ; Hemicholinium 3 - metabolism ; Male ; Maze Learning - physiology ; memory ; Memory - physiology ; Nerve Tissue Proteins - analysis ; Organ Specificity ; Rats ; Rats, Inbred F344 ; Receptors, Presynaptic - analysis ; septohippocampal system ; spatial learning ; Vertebrates: nervous system and sense organs</subject><ispartof>Neuroscience, 1999-03, Vol.89 (3), p.771-780</ispartof><rights>1998 IBRO</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-f2a8f33c96b4d5ea2df64f07a5ff1d46e984e57eff9447df99b074ccd8fab1e83</citedby><cites>FETCH-LOGICAL-c421t-f2a8f33c96b4d5ea2df64f07a5ff1d46e984e57eff9447df99b074ccd8fab1e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0306452298003741$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1657996$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10199612$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baxter, M.G</creatorcontrib><creatorcontrib>Frick, K.M</creatorcontrib><creatorcontrib>Price, D.L</creatorcontrib><creatorcontrib>Breckler, S.J</creatorcontrib><creatorcontrib>Markowska, A.L</creatorcontrib><creatorcontrib>Gorman, L.K</creatorcontrib><title>Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status</title><title>Neuroscience</title><addtitle>Neuroscience</addtitle><description>The nature of age-related changes in cholinergic function and their relationship to age-related behavioral decline were examined in the present study. Male Fischer-344 rats of four ages (four, 11, 17 and 23
months) were tested in a battery of cognitive tasks. Discrete microdissections of brain areas involved in cognitive function were performed, and activity of choline acetyltransferase and levels of hemicholinium-3 binding were determined to assess the integrity of cholinergic innervation. Age-related changes in cholinergic markers occurred predominantly in the medial septal area and its target areas (hippocampus and cingulate cortex), and were also present in the posterior caudate. However, most of the age-related changes in cholinergic markers were already present at ages at which behavioral impairment was not yet maximal. There were some consistent correlations between behavioral and neurochemical measures, independent of age, but these accounted for relatively small proportions of variance in behavioral performance. For most of these correlations, lower levels of presynaptic cholinergic markers were related to better behavioral performance. In brain areas in which correlations changed with age, lower levels of presynaptic cholinergic markers were associated with better performance in young rats, whereas higher levels were associated with better performance in aged rats.
Recent lesion studies using a toxin selective for basal forebrain cholinergic neurons have suggested that these neurons do not play as central a role in learning and memory in young and aged animals as was previously thought. When considered in this context, the present results suggest that preserved cholinergic function in old age might act indirectly to sustain cognitive ability. Changes in cholinergic function may represent one of a number of age-related neurobiological events that underlie behavioral impairments, or may be a permissive factor for other age-related processes that are more directly responsible for cognitive impairments.</description><subject>acetylcholine</subject><subject>Acetylcholine - physiology</subject><subject>ageing</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>basal forebrain</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Brain Chemistry</subject><subject>Choline O-Acetyltransferase - analysis</subject><subject>Cholinergic Agents - metabolism</subject><subject>Cognition - physiology</subject><subject>Cognition Disorders - physiopathology</subject><subject>Development. Senescence. Regeneration. Transplantation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>hemicholinium 3</subject><subject>Hemicholinium 3 - metabolism</subject><subject>Male</subject><subject>Maze Learning - physiology</subject><subject>memory</subject><subject>Memory - physiology</subject><subject>Nerve Tissue Proteins - analysis</subject><subject>Organ Specificity</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Receptors, Presynaptic - analysis</subject><subject>septohippocampal system</subject><subject>spatial learning</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0306-4522</issn><issn>1873-7544</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0V1vFCEUBmDSaNq19ifUcGGMXoyFGT4Gb4xp_Eqa2MT2mjBw2EFnmRWYmv572e5GvSs3JPCcA3kPQueUvKWEiovvpCOiYbxtX6v-DSGdZA09Qivay66RnLEnaPWXnKBnOf8gdXHWHaOT2kEpQdsVGq8T5PtotiVYvDHpJ6SMZ4_tOE8hQlrXY79EW8IccYi4jICTKXhIJsR3OMFkdld5DFv8O5QRmzVgEx228zqGEu4A52LKkp-jp95MGc4O-ym6_fTx5vJLc_Xt89fLD1eNZS0tjW9N77vOKjEwx8G0zgvmiTTce-qYANUz4BK8V4xJ55UaiGTWut6bgULfnaJX-77bNP9aIBe9CdnCNJkI85K1UEKqlpNHIZVcir5rK-R7aNOccwKvtynUqO41JXo3C_0wC70LWqteP8xC01r34vDAMmzA_Ve1D7-ClwdgsjWTTybakP85wWWFlb3fM6ix3QVIOtsA0YILCWzRbg6P_OQPq_6n3A</recordid><startdate>19990301</startdate><enddate>19990301</enddate><creator>Baxter, M.G</creator><creator>Frick, K.M</creator><creator>Price, D.L</creator><creator>Breckler, S.J</creator><creator>Markowska, A.L</creator><creator>Gorman, L.K</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>19990301</creationdate><title>Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status</title><author>Baxter, M.G ; Frick, K.M ; Price, D.L ; Breckler, S.J ; Markowska, A.L ; Gorman, L.K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-f2a8f33c96b4d5ea2df64f07a5ff1d46e984e57eff9447df99b074ccd8fab1e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>acetylcholine</topic><topic>Acetylcholine - physiology</topic><topic>ageing</topic><topic>Aging - physiology</topic><topic>Animals</topic><topic>basal forebrain</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Brain Chemistry</topic><topic>Choline O-Acetyltransferase - analysis</topic><topic>Cholinergic Agents - metabolism</topic><topic>Cognition - physiology</topic><topic>Cognition Disorders - physiopathology</topic><topic>Development. Senescence. Regeneration. Transplantation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>hemicholinium 3</topic><topic>Hemicholinium 3 - metabolism</topic><topic>Male</topic><topic>Maze Learning - physiology</topic><topic>memory</topic><topic>Memory - physiology</topic><topic>Nerve Tissue Proteins - analysis</topic><topic>Organ Specificity</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Receptors, Presynaptic - analysis</topic><topic>septohippocampal system</topic><topic>spatial learning</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baxter, M.G</creatorcontrib><creatorcontrib>Frick, K.M</creatorcontrib><creatorcontrib>Price, D.L</creatorcontrib><creatorcontrib>Breckler, S.J</creatorcontrib><creatorcontrib>Markowska, A.L</creatorcontrib><creatorcontrib>Gorman, L.K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baxter, M.G</au><au>Frick, K.M</au><au>Price, D.L</au><au>Breckler, S.J</au><au>Markowska, A.L</au><au>Gorman, L.K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status</atitle><jtitle>Neuroscience</jtitle><addtitle>Neuroscience</addtitle><date>1999-03-01</date><risdate>1999</risdate><volume>89</volume><issue>3</issue><spage>771</spage><epage>780</epage><pages>771-780</pages><issn>0306-4522</issn><eissn>1873-7544</eissn><coden>NRSCDN</coden><abstract>The nature of age-related changes in cholinergic function and their relationship to age-related behavioral decline were examined in the present study. Male Fischer-344 rats of four ages (four, 11, 17 and 23
months) were tested in a battery of cognitive tasks. Discrete microdissections of brain areas involved in cognitive function were performed, and activity of choline acetyltransferase and levels of hemicholinium-3 binding were determined to assess the integrity of cholinergic innervation. Age-related changes in cholinergic markers occurred predominantly in the medial septal area and its target areas (hippocampus and cingulate cortex), and were also present in the posterior caudate. However, most of the age-related changes in cholinergic markers were already present at ages at which behavioral impairment was not yet maximal. There were some consistent correlations between behavioral and neurochemical measures, independent of age, but these accounted for relatively small proportions of variance in behavioral performance. For most of these correlations, lower levels of presynaptic cholinergic markers were related to better behavioral performance. In brain areas in which correlations changed with age, lower levels of presynaptic cholinergic markers were associated with better performance in young rats, whereas higher levels were associated with better performance in aged rats.
Recent lesion studies using a toxin selective for basal forebrain cholinergic neurons have suggested that these neurons do not play as central a role in learning and memory in young and aged animals as was previously thought. When considered in this context, the present results suggest that preserved cholinergic function in old age might act indirectly to sustain cognitive ability. Changes in cholinergic function may represent one of a number of age-related neurobiological events that underlie behavioral impairments, or may be a permissive factor for other age-related processes that are more directly responsible for cognitive impairments.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>10199612</pmid><doi>10.1016/S0306-4522(98)00374-1</doi><tpages>10</tpages></addata></record> |
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| ispartof | Neuroscience, 1999-03, Vol.89 (3), p.771-780 |
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| subjects | acetylcholine Acetylcholine - physiology ageing Aging - physiology Animals basal forebrain Biological and medical sciences Biomarkers Brain Chemistry Choline O-Acetyltransferase - analysis Cholinergic Agents - metabolism Cognition - physiology Cognition Disorders - physiopathology Development. Senescence. Regeneration. Transplantation Fundamental and applied biological sciences. Psychology hemicholinium 3 Hemicholinium 3 - metabolism Male Maze Learning - physiology memory Memory - physiology Nerve Tissue Proteins - analysis Organ Specificity Rats Rats, Inbred F344 Receptors, Presynaptic - analysis septohippocampal system spatial learning Vertebrates: nervous system and sense organs |
| title | Presynaptic markers of cholinergic function in the rat brain: relationship with age and cognitive status |
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